A biological system is more than its components – it accomplishes a function as a synergy of these components. The primarily deconstructive approach of dissecting the system, increasingly down to molecular level, needs the complement of reconstructing functions on all levels, i.e. in our conceptualization of biology and its perturbation, in our experimental models and in computer modelling.
Toxicology knows the somewhat arbitrary subclass of “systemic toxicities” – in essence there is no relevant toxic insult or more general disease, which is not “systemic” as at least inflammation and repair will be involved. However, the more parts of the body are involved, the more there is a challenge for non-animal models.
A case is made here that we first of all need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us how to model these systems by bioengineering and in virtual computer models, i.e. a systems biology or systems toxicology approach. Noteworthy, there is now beside this computational systems biology approach also the experimental one of multi-organ-on-chip and microphysiological systems (MPS). Both bring back a more physiological view of the whole organism, allowing also to more adequately addressing systemic toxicities, i.e. the perturbation on organism level, without necessarily using substitute organisms (animals). The challenge is to establish now disease models, i.e. micropathophysiological systems (MPPS) to expand their utility from toxicology to biomedicine as a whole.